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Original Article
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5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement
Article first published online: 27 JAN 2010
DOI: 10.1002/cncr.24903
Copyright © 2010 American Cancer Society
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How to Cite
Widhalm, G., Wolfsberger, S., Minchev, G., Woehrer, A., Krssak, M., Czech, T., Prayer, D., Asenbaum, S., Hainfellner, J. A. and Knosp, E. (2010), 5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Cancer, 116: 1545–1552. doi: 10.1002/cncr.24903
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Publication History
- Issue published online: 3 MAR 2010
- Article first published online: 27 JAN 2010
- Manuscript Accepted: 21 JUL 2009
- Manuscript Revised: 9 JUL 2009
- Manuscript Received: 5 MAY 2009
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Keywords:
- diffusely infiltrating gliomas;
- nonsignificant contrast enhancement;
- 5-aminolevulinic acid;
- anaplastic foci;
- positron emission tomography;
- proliferation rate
Abstract
BACKGROUND:
Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5-Aminolevulinic acid (5-ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5-ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling.
METHODS:
5-ALA was administered in 17 patients with diffusely infiltrating gliomas with nonsignificant contrast enhancement. During glioma resection, positive fluorescence was noted by a modified neurosurgical microscope. Intraoperative topographic correlation of focal 5-ALA fluorescence with maximum 11C-methionine positron emission tomography uptake (PETmax) was performed. Multiple tissue samples were taken from areas of positive and/or negative 5-ALA fluorescence. Histopathological diagnosis was established according to World Health Organization (WHO) 2007 criteria. Cell proliferation was assessed for multiregional samples by MIB-1 labeling index (LI).
RESULTS:
Focal 5-ALA fluorescence was observed in 8 of 9 patients with WHO grade III diffusely infiltrating gliomas. All 8 of 8 WHO grade II diffusely infiltrating gliomas were 5-ALA negative. Focal 5-ALA fluorescence correlated topographically with PETmax in all patients. MIB-1 LI was significantly higher in 5-ALA–positive than in nonfluorescent areas within a given tumor.
CONCLUSIONS:
The data indicate that 5-ALA is a promising marker for intraoperative visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Unaffected by intraoperative brain shift, 5-ALA may increase the precision of tissue sampling during tumor resection for histopathological grading, and therefore optimize allocation of patients to adjuvant treatments. Cancer 2010. © 2010 American Cancer Society.